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Nucleic acids: DNA and RNA

Done ByMajed Felemban

*DNADouble helix2 chainsBuilding blocksNucleotidesDNA directsIs own replicationDirects RNA synthesis protein synthesisCampbell and Reece, P86

*In Eukaryotes (animals, plants, fungi)

*In Prokaryotes (bacteria, archaea)Main chromosome is one large, continuous loopHundreds to thousands of genesMay have smaller loops, with a few genes eachMay be swapped between bacteriaAntibiotic resistance, etc.

*ReplicationTranscriptionTranslation

*Roles of Nucleic AcidsDNAResponsible for inheritanceCodes for proteins and functional RNAsGenesRegulatory sequencesControl which genes are transcribed, and whenOther unknown functions80-90% of the human genome has no known function

Campbell and Reece, P86, 87

*Roles of Nucleic AcidsRNAInformation transmission (mRNA)Processing and transport (tRNA, rRNA, snRNA)Catalytic (ribozymes)Regulation and feedback (siRNA)Unit of inheritance (retroviruses)Other?

Campbell and Reece, P86, 87

*Nucleic Acid chemistry is the same for all life on earth.DNA & RNA are polymers of monomers - nucleotides.Each nucleotide has three components(Deoxy)ribonucleic AcidNUCLEIC ACID STRUCTURESCampbell and Reece, 862. (DEOXY)RIBOSE SUGAR = STRUCTURAL3. NITROGENOUS BASES = INFORMATIONALXX1. PHOSPHORIC ACID = STRUCTURAL

*Campbell and Reece, P87

*Phosphoric Acid & Related CompoundsPhosphoric acid isTriprotic.Reacts with CHOs or alcohols to form esters.D

*Phosphoric Acid & Related CompoundsPhosphoric acid isTriprotic.Reacts with alcohols to form esters.

*The sugar may be Ribose (in RNA) or Deoxyribose (in DNA) RiboseDeoxyribosePhosphate can covalently bond to C3 and C5Bases (A,C,G,T or U) can covalently bond to C1

*Bases in DNA and RNA

*A Base Joined To A Ribose SugarIs Called A NucleosidePyrimidines bond at N-1 to C-1Purines bond N-9 to 1 Carbon of sugarThe carbons in the ribose are now designated as C prime (or C) to distinguish them from those in the base.or Hor H

*When Phosphate is Bound to a Nucleoside it is Called a NucleotideATP, GTP, CTP, UTP (NTPs) are substrates for RNA synthesisdATP, dGTP, dCTP, dTTP (dNTPs) are substrates for DNA synthesis

*Mononucleotides as they Occur in DNA & RNADNARNAA,C,G or T (DNA)orA,C,G or U (RNA)All nucleotides are asymmetrical

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Four Nucleotides With 5 to 3 Phosphodiester LinkagesDNA & RNA are Polymers of NucleotidesAll DNA and RNA polymers are asymmetrical with 5 to 3 direction.

*Properties of DNA and RNAThey may be informational eg genomic DNA, mRNA.They may be structural eg rRNA & tRNA.Retain 5& 3 molecular orientation due to nucleotide asymmetry.They are often single stranded (typically RNA).They may be extremely long. Movie*Two polymers (or strands) may become double stranded when certain conditions are met ie they are antiparallel & complementary in nucleotide sequence (typically nuclear DNA).* Terao et al., 2008: Lab on a chip DOI: 10.1039/b803753a

*Duplex DNA is AntiparallelDuplex DNA is NEVER Parallel!or5335or

*Duplex DNA has Complementarity because of Hydrogen BondsH bonds are weak (~1/20th of a covalent bond):Often allows transient contact between molecules (biological signalling systems).May allow stable contact that can be disrupted and reformed (eg DNA).

*Hydrogen BondsForm between O &/or N with H between them eg O-HO, NH-N or O-HN.Are due to electrostatic forces. H is slightly +ve. O &/or N are slightly -ve.Are very weak compared to covalent bondsMay be broken & reform under various chemical or physical conditions.

* Two representations of duplex DNA showing:H bonds between bases and,Covalently bonded Sugar Phosphate backbones.~10 basepairs per turn of the helix.Duplex DNA width = 2nm.

*Double Stranded (or Duplex) DNAIs characteristic of genomic DNA.Consists of two separate nucleic acid polymers (strands).The two strands are Antiparallel wrt 5& 3 ends.They are held together by Hydrogen Bonds between the bases.H-Bond energies are weak BUT there are many of them which makes the duplex DNA very stable.Bases are Complementary such that: A always pairs with T (2 H Bonds). C always pairs with G (3 H Bonds).Two strands of complementary antiparallel DNA form a Double Helix eg as found in a chromosome.

*History of The Double Helix of DNAThe structure of the double helix was found by Rosalind Franklin using X-ray crystallography and correctly interpreted by Watson & Crick in 1953 who also used Chargaffs rule.The bases are Hydrophobic and are in the Centre of the helix where complementary bases pair via H-bonding.The Ribose Sugar and Phosphate groups are on the Outside of the helix where they can H bond to polar solvents like water.

*Xray diffraction pattern of DNA similar to Franklins data (above, 1953). Watson & Cricks structure for DNAKey data that Watson & Crick worked withChargaffs Rule: there is a 1:1 ratio of purines to pyrimidines (because A=T, GC always).

*Plasmodium = malaria*When the pH is the same as the pKa then half of the time the group is OH and the other half O- ie 1:1 ratio1 pH unit above the pKa then 1/10th of the time as OH and 9/10ths as O- ie 1:10 ratioBased on weak acid formula: pH = pKa +log([base]/[acid])Formation of esters is a condensation reaction.Furthermore:P is a weak acid because it does not completely dissociate in H2O.Ka = the dissociation constantweak acids usually have a pKa less than 1pKa = negative log of the Kathe element is phosphorousPhosphoric acid = Pi = inorganic phosphateOrganic phosphate is attached to a Carbon containing molecule like ATP etc*Adenosine triphosphate (base = adenine) nuc'tide = AdenylateGuanosine triphosphate (base = guanine) nuc'tide = GuanylateCytidine triphosphate (base = cytosine) nuc'tide = CytidylateThymidine triphosphate (base = thymine) nuc'tide = ThymidylateUridine triphosphate (base = uracil) nuc'tide = Uridylate*The smallest human chromosome, fully extended, would stretch around 1.7cm, the longest around 8.5cm. All the DNA in a normal human cell, stretched end to end, would extend more than two metres.Width of the double helix: ~2nm. Width of a human forefinger: ~2cm. If scaled up to this width, the shortest human chromosome when fully extended would stretch 170 kilometres; the longest 850 km. Total cellular DNA would be 20,000 kilometres.**~10kJ per mole cf 300-400 for single covalent, 600 for double